The research outlined in this proposal is designed to elucidate the biochemical and genetic mechanisms underlying the expression of a series of unique aldehyde dehydrogenase isozymes found only in rat hepatomas generated by carcinogenic aromatic amines. The specific aims are: 1. To determine if the new aldehyde dehydrogenase isozymes generated during 2-acetylamino-fluorene-induced hepatocarcinogenesis are the result of (a) derepression of gene(s) for AlDH not normally expressed in rat liver or (b) gene derepression and epigenetic modification of newly synthesized and/or previously existing AlDH monomers. (Enzyme purification, physical, functional and immunochemical characterization, reversible denaturation and freeze-thaw hybridization studies.) 2. To determine whether the expression of the hepatoma-specific aldehyde dehydrogenase phenotype is (a) the result of altered liver metabolism including a rearrangement of gene expression and/or regulation due directly to the administration of carcinogen or (b) the result of transformation-associated stable changes induced in the cells affected by carcinogen. (Time-course study for the appearance of tumor-specific AlDH, physical and immunochemical characterization, histopathological identification of lesions.) Completion of these specific aims will result in the first detailed description of the biochemical and genetic events underlying a specific phenotypic modification associated with the neoplastic transformation.